A Phase 2 Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Subjects With Indolent Non-Hodgkin Lymphoma

Indolent Non-Hodgkin Lymphoma Clinical Trial

— TEMPO  

Official title:

A Phase 2, Randomized, Open-label, 2-Arm Study Comparing 2 Intermittent Dosing Schedules of Duvelisib in Subjects With Indolent Non-Hodgkin Lymphoma (iNHL)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04038359
• Other study ID #: VS-0145-229
• Secondary ID: 2019-001381-14
• Status: Completed
• Phase: Phase 2
• Start date: September 24, 2019
• Est. completion date: July 24, 2023

Study information

• Verified date: February 2024
• Source: SecuraBio
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will examine the effects of predefined 2-week duvelisib dose holidays on tumor responses and safety/tolerability.

Description:

This is a Phase 2, randomized, open-label, 2-arm study designed to evaluate the efficacy and safety of prescribed drug holidays of duvelisib treatment in subjects with R/R iNHL who have received at least 1 prior systemic therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 102
• Est. completion date: July 24, 2023
• Est. primary completion date: July 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Age = 18 years, ECOG performance status = 2
• Histologically confirmed diagnosis of iNHL (Subtypes include FL Grades 1 to 3a, marginal zone lymphoma (splenic, nodal, or extranodal), or SLL
• Must have received 1 prior systemic regimen for iNHL
• Must have documented radiologic evidence of disease progression, at least 1 bi-dimensionally measurable lesion = 1.5 cm (which has not been previously irradiated), according to 2007 revised IWG criteria, and be a candidate for a subsequent line of therapy.
• Must have adequate organ function defined by the following laboratory parameters:
• Absolute neutrophil count (ANC) = 1.0 × 10^9/L
• Platelet count = 75 × 10^9/L
• Hemoglobin = 8 g/dL
• Estimated creatinine clearance = 60 mL/min, as determined by the Cockcroft-Gault method
• Total bilirubin = 1.5 × upper limit of normal (ULN) (exception: subjects with Gilbert's Syndrome may have a bilirubin > 1.5 × ULN)
• Aspartate transaminase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum pyruvic transaminase (SGPT) = 3.0 × ULN

Exclusion Criteria:

• Anticancer treatment, major surgery, or use of any investigational drug within 28 days before the start of study intervention; palliative radiation therapy is allowed if > 7 days before planned first dose of study interventions, and any toxicity is Grade = 1
• Clinical or histological evidence of transformation to a more aggressive subtype of lymphoma or grade 3b FL or Richters' transformation or CLL
• Prior allogeneic hematopoietic stem cell transplant (HSCT); prior treatment with a PI3K inhibitor
• History of drug-induced colitis or pneumonitis; TB treatment = 2 years prior to randomization; administration of a live or live attenuated vaccine within 6 weeks of randomization
• Ongoing treatment with chronic immunosuppressants or systemic steroids or treatment for systemic bacterial, fungal, or viral infection
• Active cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection
• Unable to receive prophylactic treatment for pneumocystis, herpes simplex virus (HSV), or herpes zoster (VZV) at screening
• Concurrent administration of medications or foods that are strong inhibitors or inducers of cytochrome P450 3A (CYP3A). No prior use within 2 weeks before the start of study intervention.
• Baseline QTcF > 500 ms
• Concurrent active malignancy other than non-melanoma skin cancer or carcinoma in situ of the cervix, bladder cancer, or prostate cancer not requiring treatment. Subjects with previous malignancies are eligible if they have been disease-free for 2 years or more.
• Unstable or severe uncontrolled medical condition that would, in the Investigator's judgment, increase the subject's risk to participating in this study.

Related Conditions & MeSH terms

• Indolent Non-Hodgkin Lymphoma
• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Duvelisib
PI3K Inhibitor

Locations

Country	Name	City	State
Czechia	FN Hradec Kralove	Hradec Králové
Czechia	Vseobecna fakultni nemocnice v Praze	Praha 2
Germany	Universitaetsklinikum Bonn AöR	Bonn
Italy	Oncology Istituto Romagnolo per lo Studio dei Tumori (IRST) Dino Amadori	Meldola	Forli
Italy	IEO - Istituto Europeo di Oncologia, IRCCS	Milano
Italy	AUSL di Reggio Emilia IRCCS, Arcispedale Santa Maria Nuova di Reggio Emilia	Reggio Emilia
Italy	Azienda Ospedaliera Santa Maria di Terni	Terni
Italy	Ospedale di Circolo, PO Varese, AO Ospedale di Circolo e Fondazione Macchi	Varese
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center - Oncology	Seoul
Korea, Republic of	Samsung Medical Center - Hematology-Oncology	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Poland	Pratia Onkologia Katowice	Katowice
Poland	Centrum Medyczne Pratia Poznan	Skórzewo
Poland	Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o.	Slupsk	Pomorskie
Russian Federation	City Clinical Hospital n.a. Botkin	Moscow
Russian Federation	State Budgetary Healthcare Institution of Moscow City Moscow Multidisciplinary Clinical Center "Kommunarka" of the Department of Healthcare of Moscow City	Moscow
Russian Federation	First Saint-Petersburg State Medical University n.a. I.P. Pavlov	Sankt-Peterburg
United Kingdom	NHS Greater Glasgow & Clyde - CRUK Clinical Trials Unit	Glasgow
United Kingdom	Royal Liverpool Hospital [Hematology/Transfusion Medicine]	Liverpool
United Kingdom	Christie Hospital NHS Foundation Trust	Manchester
United States	Robert H. Lurie Comprehensive Cancer Center	Chicago	Illinois
United States	Florida Cancer Specialists - Fort Myers	Fort Myers	Florida
United States	Comprehensive Cancer Centers of Nevada	Las Vegas	Nevada
United States	Florida Cancer Specialists & Research Institute - Lecanto	Lecanto	Florida
United States	Tennessee Oncology	Nashville	Tennessee
United States	Mid-Florida Cancer Centers	Orange City	Florida

Sponsors (1)

Lead Sponsor	Collaborator
SecuraBio

Countries where clinical trial is conducted

United States,  Czechia,  Germany,  Italy,  Korea, Republic of,  Poland,  Russian Federation,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	ORR (Overall Response Rate)	Proportion of subjects achieving a CR or PR will be estimated as per IWG Criteria.	14 months
Secondary	PFS (Progression-free Survival)	From time of first dose of study intervention to PD or death.	2 years
Secondary	ORR (Overall Response Rate)	Proportion of subjects achieving a CR or PR will be estimated as per IWG Criteria and Lugano Criteria	ORR estimated at 6, 12, 18, and 24 months after first dose of study intervention.
Secondary	DOR (Duration of Response)	From the time of first response to PD using KM methods.	2 years
Secondary	OS (Overall Survival)	From time of first dose of study intervention to death.	2 years
Secondary	LNRR (Lymph Node Response Rate)	LNRR will be calculated as the proportion of subjects achieving = 50% decrease in the SPD of target lymph nodes.	14 months
Secondary	TTFR (Time To First Relapse)	From the time of first dose of study intervention to time of first CR or PR.	14 months
Secondary	Number of participants with treatment-emergent adverse events as assessed by CTCAE v5.0	From the time of screening to the end of Safety Follow-Up period of the study.	14 months
Secondary	Peak Plasma Concentration (Cmax)		14 months
Secondary	TTF (Time To Treatment Failure)	From first dose of study intervention until discontinuation for any reason and will be summarized using KM methods.	2 years
Secondary	Area under the plasma concentration versus time curve (AUC)		14 months